Airway inflammation represents a major cause of disability and death. Chronic obstructive bronchitis and emphysema, together known as chronic obstructive pulmonary disease (COPD) affects 600 million people world-wide, with some three million dying from the disease each year. Asthma is also very common, affecting 155 million people worldwide. Together the global market for these diseases is in excess of US$10 billion. Targeting inflammatory mediators represents a well-accepted strategy for the treatment of asthma. The same is true for COPD.  One of the problems associated with targeting inflammatory mediators is the complexity and the multiplicity of the immune system. For example asthma, which is mediated by Th2 lymphocytes, is characterized by increases in interleukin-4 (IL-4), IL-5, IL-9 and IL-13. Thus selection of the most appropriate target(s) has been the subject of considerable debate. On the other hand the immune system plays a crucial part in host defense and targeting components of this system for the treatment of diseases such as asthma could produce unacceptable side-effects. Histone (de)acetylation represents one strategy by which multiple cytokines could be targeted and in selected organs. It is now well accepted that the genome is plastic and its structure can determine the level of transcription. Two families of enzymes, histone deacetylases (HDACs) and histone acetyl transferases (HATs) control genome structure and modifying the activity of these enzymes regulates gene expression. In our recent report describing the therapeutic potential of HDAC inhibitors we analyze this drug class and describe how candidates can be used to regulate gene expression in a highly specific fashion. To date molecules that modulate HDAC and HAT activity have been primarily envisaged as possible treatments of cancer, however recent studies suggest that asthma may also represent a target. Field-leaders at the National Heart and Lung Institute in London have examined the expression and activity of HATs and HDACs in bronchial biopsies from normal subjects and subjects with asthma. These authors report that subjects with asthma had reduced HDAC enzymatic activity and reduced HDAC1 and HDAC2 protein expression and increased HAT activity. These changes were reversed by inhaled steroids and were suggested to underlie the increased expression of multiple inflammatory genes in asthma. This study therefore suggests that companies involved in airway disease should evaluate histone acetylation as a candidate therapeutic target.

Adapted from Ito et al, Am J Respir Crit Care Med 2002 Aug 1;166(3):392-6

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